I decided to read up on ricin, to refresh my memory, and found more details on its mechanisms than I had known before. Read on, boys and girls, to discover a toxin that is so efficient it's almost like it was engineered to be the world's most potent poison...
It consists of two pieces: ricin A and ricin B. Many plants (such as barley) have ricin A without ricin B.
Ricin A is the enzyme part, the piece that does the dirty work. It cleaves a certain, universal loop on the large subunit of a ribosome, neatly snipping it into inactivity. Since ribosomes are the proteins which make every protein in the cell, the cell shuts down if too many ribosomes are snipped.
Each unit of ricin A can inactivate 1500 ribosomes per minute. It resists degradation by the cell: the harsh environments of lysosomes and endosomes (the cell's incinerators) don't affect it, and it resists tagging for destruction (ubiquitination) by lacking the particular amino acid that the tag is usually attached to.
Ricin B is the transportation part, which is the crucial element that makes it toxic. It binds to receptors on the cell surface, and gets sucked into the cell by a normal cell process (the aforementioned endosomes). It's dumped in the usual place for endosomes, travels up the Golgi in reverse, and makes it to the end in the endoplasmic reticulum (ER). Chaperone molecules in the ER, where many proteins are made, look at it and say "whoops, mis-folded protein, eject it into the main part of the cell for degradation." Once it's in the main part of the cell, the cytosol, it's free to let ricin A do its work on free-floating ribosomes.
So we have a toxin which moves freely into (and somehow out of) cells, using their own transportation machinery, resists all the cell's degradation pathways, gets put exactly where it needs to be without effort, hits a universal spot on quite possibly the most important protein in the cell and disables it immediately, and can do so thousands of times a minute for many minutes. I can't think of any way I'd engineer a better poison, except to make it possible to absorb it in some way other than ingestion or injection. (DMSO, anyone?)
The more I learn about it, the scarier it gets.
It consists of two pieces: ricin A and ricin B. Many plants (such as barley) have ricin A without ricin B.
Ricin A is the enzyme part, the piece that does the dirty work. It cleaves a certain, universal loop on the large subunit of a ribosome, neatly snipping it into inactivity. Since ribosomes are the proteins which make every protein in the cell, the cell shuts down if too many ribosomes are snipped.
Each unit of ricin A can inactivate 1500 ribosomes per minute. It resists degradation by the cell: the harsh environments of lysosomes and endosomes (the cell's incinerators) don't affect it, and it resists tagging for destruction (ubiquitination) by lacking the particular amino acid that the tag is usually attached to.
Ricin B is the transportation part, which is the crucial element that makes it toxic. It binds to receptors on the cell surface, and gets sucked into the cell by a normal cell process (the aforementioned endosomes). It's dumped in the usual place for endosomes, travels up the Golgi in reverse, and makes it to the end in the endoplasmic reticulum (ER). Chaperone molecules in the ER, where many proteins are made, look at it and say "whoops, mis-folded protein, eject it into the main part of the cell for degradation." Once it's in the main part of the cell, the cytosol, it's free to let ricin A do its work on free-floating ribosomes.
So we have a toxin which moves freely into (and somehow out of) cells, using their own transportation machinery, resists all the cell's degradation pathways, gets put exactly where it needs to be without effort, hits a universal spot on quite possibly the most important protein in the cell and disables it immediately, and can do so thousands of times a minute for many minutes. I can't think of any way I'd engineer a better poison, except to make it possible to absorb it in some way other than ingestion or injection. (DMSO, anyone?)
The more I learn about it, the scarier it gets.
no subject
Date: 2008-12-24 06:51 (UTC)no subject
Date: 2008-12-24 13:59 (UTC)And it's estimated that as much as the size of a grain of salt can be lethal.
I looked it up after an episode of CSI. Amazing what you learn from that show.
Odzywki
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